1. Field Of The Invention
This invention relates to a new method of preparing aromatic acetamides from aryl methyl ketones.
2. Background Information And Description Of The Related Art
The following information is disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98.
Aromatic acetamides are useful as intermediates in the production of various chemicals and pharmaceuticals. For example, 4-hydroxyphenylacetamide is an intermediate in the production of atenolol, a well-known beta-adrenergic blocker.
The Willgerodt reaction is known in the art as the reaction between an aryl alkyl ketone and aqueous yellow ammonium polysulfide to produce an aromatic amide having the same number of carbon atoms. For example, by means of this reaction, 4-hydroxyphenylacetamide may be produced from 4-hydroxyacetophenone.
In addition to aryl alkylketones, the reaction has been stated to be applicable to the production of amides from other compounds, such as dialkyl ketones, aliphatic mercaptans, secondary and tertiary alcohols, acetals, and aromatic hydrocarbons. It has also been stated that a mixture of sulfur and ammonia is equivalent to ammonium polysulfide in obtaining the reaction.
In the Kindler modification of the Willgerodt reaction, the aryl alkyl ketone or other reactant is reacted with an amine and sulfur in an anhydrous system. However, as described in the art, the product in this modification is not the amide but the thioamide.
Description of the foregoing reactions are exemplified in the following references.
U.S. Pat. No. 2,459,706 issued Jan. 18, 1949 to J. A. King, discloses the production of amides by subjecting aliphatic mercaptans or secondary or tertiary alcohols to a Willgerodt reaction with ammonium polysulfide, or sulfur and ammonia or an amine. In column 3, lines 5 to 7, the patentee states that "When substantially anhydrous conditions prevail, the carboxylic derivative resulting is a thioamide . . . . "
U.S. Pat. No. 2,572,809 issued Oct. 23, 1951 to C. F. Jelinek, discloses the Willgerodt reaction between acetals and ammonium polysulfide, or ammonium hydroxide and sulfur in an aqueous system, or a primary or secondary amine and sulfur in an anhydrous system, to produce amides. Example 5 in column 3 of the patent shows the reaction between dimethyl benzal, sulfur and morpholine to produce a thioamide, viz., 4-thiobenzoylmorpholide.
U.S. Pat. No. 2,610,980 issued Sept. 16, 1952 to M. A. Naylor, teaches the formation of amides by reacting aromatic hydrocarbons with ammonium polysulfide, or sulfur and ammonia in the presence of water or under anhydrous conditions. In column 5, lines 35 to 37, the patentee states, "When substantially anhydrous conditions prevail, the carboxylic acid derivative resulting is a thioamide."
U.S. Pat. No. 2,689,246 issued Sept. 14, 1954 to H. Feichtinger, discloses the Willgerodt reaction of unsaturated nitrocompounds with ammonium polysulfide, or ammonia or an amine and sulfur, in aqueous system to form a carboxylic acid amine, or in anhydrous system to form a corresponding thioamide.
German Patent No. 405,675, granted Nov. 4, 1924 to K. Kindler, discloses generally the preparation of thioamides by reacting aldehydes or ketones with ammonia or a primary or secondary amine, and sulfur. However, in the only specific example utilizing ammonia gas, benzaldehyde is reacted to form thiobenzamide.
E. V. Brown, "The Willgerodt Reaction" in Synthesis 1975, June 1975, 358-375, discloses the Willgerodt reaction of various aryl methyl ketones and other compounds with ammonium polysulfide, or sulfur and ammonium hydroxide in aqueous system to produce aryl acetamides, or with sulfur and an amine such as morpholine in a Willgerodt-Kindler reaction to produce thioamides.
M. Carmack and M. A. Spielman, "The Willgerodt Reaction", Chapter 2 of R. Adams, Editor, Organic Reactions, Vol. III, (New York: John Wiley, 1946), 83-107, disclose the Willgerodt reaction of several methyl aryl ketones with ammonium polysulfide, or sulfur and aqueous ammonia to produce aromatic acetamides, and also show examples of the Kindler modification involving the reaction of any of various methyl aryl ketones with sulfur and amines in anhydrous system to produce acetothioamides. This reference also states that anhydrous ammonia sometimes is used (page 85), citing German Patent No. 405,675 described previously.
A. C. Ott, et. al., J. Amer. Chem. Soc. 68 (1946): 2633-2634, discloses the preparation of p-hydroxyphenylacetamide by the Willgerodt reaction of p-hydroxyacetophenone and ammonium sulfide in aqueous system.